Biomedical Sciences ETDs

Publication Date

Fall 11-18-2019

Abstract

Members of the Neuron-Specific Gene family (NSG1-3) play critical roles in excitatory synaptic transmission via regulation of AMPA receptor surface expression within the post-synaptic density (PSD). While NSG1 and NSG3 regulate AMPAR recycling and endocytosis, respectively, the function of NSG2 has remained elusive. Here we undertook a series of studies to assess the role of NSG2 in excitatory synaptic transmission. We found that a portion of NSG2 punctae localized with HOMER1 and surface AMPARs at excitatory synapses and that NSG2 AMPAR subunits in mouse brain. Knockout of NSG2 selectively impaired the frequency of AMPA mEPSCs, while overexpression caused a significant increase in the amplitude of AMPA mEPSCs. Despite the fact that NSG2 is actively trafficked, both static and extended timelapse (3 hr) imaging revealed that NSG2 was stably localized at ~30% of glutamatergic PSDs. Interestingly, this subset appeared largely non-overlapping with NSG1. Furthermore, endogenous NSG2 was associated with greater AMPAR surface expression that appeared to be independent of neuronal activity. Together, these data reveal that NSG2 is an AMPAR-binding protein that is required for normal synapse formation and/or maintenance. In addition, they suggest a novel type of postsynaptic diversity via selective incorporation of NSG1 and NSG2.

Keywords

Neuron specific gene, post synaptic density, AMPA receptors, protein trafficking, synapse formation and plasticity, glutamatergic neurotranmission

Document Type

Dissertation

Language

English

Degree Name

Biomedical Sciences

Level of Degree

Doctoral

Department Name

Biomedical Sciences Graduate Program

First Committee Member (Chair)

Jason P. Weick

Second Committee Member

Kevin Caldwell

Third Committee Member

Angela Wandinger-Ness

Fourth Committee Member

Nora Perrone-Bizzozero

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